Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies

Leuk Res. 2013 Nov;37(11):1461-7. doi: 10.1016/j.leukres.2013.07.034. Epub 2013 Aug 6.

Abstract

Akt, a serine/threonine protein kinase, is constitutively phosphorylated and hyperactivated in multiple cancers, including acute myeloid leukemia. High levels are linked to poor survival and inferior responses to chemotherapy, making Akt inhibition an attractive therapeutic target. In this phase I/II study of TCN-PM, a small-molecule Akt inhibitor, TCN-PM therapy was well tolerated in patients with advanced hematological malignancies, and reduced levels of phosphorylation of Akt and its substrate Bad were shown, consistent with inhibition of this survival pathway and induction of cell death. Further investigation of TCN-PM alone or in combination in patients with high Akt levels is warranted.

Trial registration: ClinicalTrials.gov NCT00642031.

Keywords: AML; Akt; Nucleoside analog; Phase I clinical trial; Triciribine.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acenaphthenes / pharmacokinetics*
  • Acenaphthenes / pharmacology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects*
  • Blotting, Western
  • Female
  • Follow-Up Studies
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / pathology
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation / drug effects
  • Prognosis
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Ribonucleotides / pharmacokinetics*
  • Ribonucleotides / pharmacology*
  • Tissue Distribution
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Acenaphthenes
  • Ribonucleotides
  • triciribine phosphate
  • Proto-Oncogene Proteins c-akt

Associated data

  • ClinicalTrials.gov/NCT00642031